More than 24,000 women in the United States are diagnosed with ovarian cancer every year, and half of these women die from their disease. Despite advances in screening and treatment, the lack of understanding of the underlying etiology has limited prevention strategies. A typical Western diet, which is high in meats and low in vegetables, may be positively associated with ovarian cancer incidence. An imbalance of omega 3 (OM-3FA) and omega 6 (OM-6FA) fatty acids contributes to excess cancer risk. Studies indicate that populations that consume high amounts of OM-3FA have lower incidences of breast, prostate and colon cancers than do those that consume less OM-3FA. Thus increasing the consumption of OM-3FA may be a nontoxic way to prevent ovarian cancer, augment cancer therapy and to significantly increase life span. Flax seed is an excellent source of dietary fiber, the OM-3FA alpha-linolenic acid (ALA), as well as lignans, which are potent anti- estrogens that have been shown to have anti-proliferative and pro-apoptotic activities in certain cancers. The proposed studies will test the effectiveness of a flax seed enriched diet, and examine the mechanism of action of OM-3FA and enteroestrogens using the laying hen as a model of ovarian carcinoma. With the exception of the aging hen, there are no other animal models of spontaneous epithelial ovarian cancer that mimic the human disease. We hypothesize that a flax seed enriched diet will reduce the incidence of ovarian carcinoma in the laying hen. Identification of molecular targets whose expression is affected by flax enriched diet will provide insight into the etiology of ovarian cancer and will provide the foundation for developing functional food based dietary intervention for the prevention and treatment of ovarian cancer in women. Three Specific Aims are proposed: 1) Determine the effective dose range of flax seed added to the hen diet that reduces the incidence of ovarian cancer; 2) Determine the effect of flax seed diet on inflammation and prostaglandin- associated mechanisms involved in ovarian cancer; 3) Determine the effect of flax seed diet on estrogen- associated mechanism involved in ovarian cancer. There is considerable public interest in the use of OM-3FA to reduce cancer and the hen model provides an important opportunity to investigate the efficacy of dietary intervention in the prevention of ovarian cancer. Relevance: Research into ovarian cancer, a highly lethal disease, has been limited by the lack of suitable animal models, because, with the exception of the laying hen, no other animals are inflicted with the same type of ovarian cancer that affects women. Using the hen as our model we will investigate the use of omega-3/flax seed diet as a way to prevent ovarian cancer. [unreadable] [unreadable] [unreadable]